Changes in mRNA and protein levels of nicotinic acetylcholine receptors in Diazoxon exposed pC12 cells

Effects of diazoxon on the gene and protein expression of nicotinic acetylcholine receptors (nAChR) were evaluated in PC12 cells. Cells were exposed to 100 μM diazoxon for 48 h in the presence versus absence of nAChR agonists or antagonists. Diazoxon significantly inhibited AChE activity in the cells. At the mRNA level, transcripts of the α4 and β2 subunits of nAChR were significantly reduced in cells exposed to diazoxon, but there was no change in α7 subunit mRNA content. Diazoxon exposure also significantly reduced the protein levels of both α4 and β2 nAChR subunits. Treatment with nicotine (10 μM) or with the nicotinic receptor antagonists, mecamylamine (10 μM) or dihydro-β-erythroidine (DHβE) (5 μM) efficiently prevented the diazoxon-induced reduction in α4 and β2 nAChR mRNA and protein in PC12 cells, but carbamaylcholine, a weak nAChR agonist, was ineffective. These data suggest that α4β2 nAChRs are involved in diazoxon-related toxicity and that nicotinic receptor antagonists could play a protective role against organophosphate-related damage.